Table 3.

Session 3: Enhancing models and manufacturing

Topic	Needed knowledge and strategies
Animal model scale	Large animal models may be more informative than rodent models to assess vector distribution and estimate appropriate dosing in humans; parallel studies conducted in both mice and a large animal model using the same capsid, promoter, vector preparation, delivery route, and normalized dose so that all the variables are standardized would facilitate translation across species.
	Take advantage of the increased lifespan of large animal models to understand how to enable re-administration of CNS-directed gene-targeted therapies.
Animal models of immune response	Identify or develop the appropriate animal models that predict the human immune response to capsids and transgene-encoded proteins; a prerequisite might be a better understanding of the immune systems of larger animal models to determine whether they are an appropriate representation of the human response.
	Develop better tools to detect and monitor the immune response in large animal models.
	Testing AAV administration in NHPs paired with immunosuppression protocols that may be used in clinical trials could yield new important information.
AAV manufacturing	Address manufacturing challenges, including capacity, cost, complexity, and diversity of the available production systems and standards for the identification and measurement of critical quality attributes of the final product.
Batch production for ultra-rare diseases	Consider the unique complexities to developing gene-targeted therapies for ultra-rare diseases and how to advance the therapeutics in a timely way where they are held to the same safety standards as those for common disorders, but maybe not the same regulatory standards in terms of the requirement for multiple manufacturing runs for licensing; this could possibly be accomplished through collaboration with the FDA.
	Develop a CMC platform for ultra-rare disorders.